| First Author | Miyawaki K | Year | 2002 |
| Journal | Nat Med | Volume | 8 |
| Issue | 7 | Pages | 738-42 |
| PubMed ID | 12068290 | Mgi Jnum | J:77483 |
| Mgi Id | MGI:2181855 | Doi | 10.1038/nm727 |
| Citation | Miyawaki K, et al. (2002) Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8(7):738-42 |
| abstractText | Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. The Gipr(-/-) mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs. |
